It has been suggested that resected liver is not only the target of a factor responsible for regeneration but is also the source of its production. During the past year we have investigated this possibility in vivo by utilizing a new model for connecting a transplanted liver in tandem with the host liver in the rat. In this preparation the host portal vein is transected and the segment coming from the intestine is anastomosed end-to-end to the portal vein of the transplant. The inferior vena cava as it leaves the transplant liver is connected to the portal vein as it enters the host liver. Such a preparation provides in vivo organ perfusion eliminating the artificiality of the in-vitro technic employed by others. Moreover, this preparation eliminates the dissimilarity of blood flow through the two liver masses; a problem which has complicated other models utilizing auxiliary or "split liver" preparations. Utilizing this model, liver regeneration was evaluated when (a) a partial (30 percent) liver transplant was connected in tandem with host liver, (b) a whole liver transplant was connected in tandem with host liver, (c) a 65 percent transplant was connected in tandem with an intact host liver, (d) a 30 percent transplant was connected in tandem with an intact host liver and a 70 percent PH was performed on the host liver 5 to 7 days after transplant, and (e) a 30 percent liver transplant was connected in tandem with a host liver subjected to 70 percent hepatectomy. Results of measurement of DNA synthesis in host livers fail to support the origin of a factor in regenerating liver itself. During the coming year investigations will be directed toward (a) elucidating the role of bile in hepatic regeneration, (b) determining if ileal isolation will result in a decrease in DNA synthesis by the PH liver connected in tandem, (c) pursuit of studies indicating that perfusion of the ileal loop with saline may restore the DNA synthesis of the PH liver abrogated by the creation of an isolated ileal loop, and (d) starting investigations relative to the role of the pancreas in liver regeneration as outlined in our original proposal.